Summary of work: We are studying the feasibility of tissue engineering of cartilage. Following up on our original observations with embryonic mesenchymal cells we have now shown conclusively that adult rabbit and aged human articular chondrocytes can be phenotypically modulated and expanded in vitro with growth factors. Importantly, these cells retain the capacity to form hyaline cartilage when re-introduced into animals. These secondary chondroprogentior cells may be useful for cell-based repair of cartilage defects. We have extended this line of research toward the development of an NMR compatible hollow fiber bioreactor (HFBR) model of cartilage formation. Our intitial studies show that primary chondrocytes and secondary chondroprogenitor cells form abundant 3-dimensional cartilage tissue in the HFBR based on histochemical and biochemical analysis. In addition, we have determined that the cartilage formation can be monitored by NMR imaging and spectroscopy. We are now studying the effects of growth factors and cytokines on cartilage formation in this model. Our goal is to optimize this system for maintaining human cartilage and utilize it as a model system for studying cartilage development, maintenance, and turnover. Another line of research has demonstrated that an immortalized chondrocyte line developed in our laboratory displays a similar pattern of matrix metalloproteinase (MMP) expression upon cytokine stimulation as has been described in human OA. This cell line will be useful for identifying inhibitors of MMP expression by chondrocytes and studying the mechanisms involved in regulating MMP expression and activation.